This blog is a little effort to make biotechnology concepts simplified to all the students in the degree classes from all the universities.I took the initiative to make concise and well formulated notes supported with the diagrams.I have struggled a lot in making notes and searching for the concepts by digging library books and surfing various sites. All i want is to create one place where you can look up to biotechnology notes and rely upon them as i have put up a lot of effort on them.

Thursday, 7 December 2017

FED BATCH KINETICS

FED BATCH KINETICS

Fed Batch as the name indicates means batch cultures which need to be fed continuously, with medium without removing culture fluid. The
culture broth is harvested usually only at the end of the operational period, either
fully or partially (the remainder serving as the inoculum for the next repeated run).
This process may be repeated (repeated fed-batch) a number of times if the cells are
fully viable and productive. Thus, there are one or more feed streams but no effluent
during the course of operation. Sources of carbon, nitrogen, phosphates, nutrients,
precursors, or inducers are fed either intermittently or continuously into the culture
by manipulating the feed rates during the run. The products are harvested only at
the end of the run. Therefore, the culture volume increases during the course of
operation until the volume is full. Thereafter, a batch mode of operation is used
to attain the final results. Thus, the fed-batch culture is a dynamic operation. By
manipulating the feed rates, the concentrations of limiting nutrients in the culture
can be manipulated either to remain at a constant level or to follow a predetermined
optimal profile until the culture volume reaches the maximum, and then a batch
mode is used to provide a final touch. In so doing, the concentration of the desired
product or the yield of product at the end of the run is maximized. This type of
operation was first called a fed-batch culture or fed-batch fermentation. The fed-batch culture has been practiced since the early 1900s, when it was recognized
in yeast production from malt wort that the malt concentration in the medium
had to be kept low enough to suppress alcohol formation and maximize the yield of
yeast cells. High malt concentration would accelerate the cell growth, which in turn
would cause anaerobic conditions that favored ethanol formation and lowered the
yield of yeast cells. Additional wort was added at a rate that was always less than
the rate at which the yeast cells could use it. Intermittent or incremental feeding of
nutrients to an initially dilute medium was introduced thereafter in large-scale yeast
production to improve the yeast yields while obviating the production of ethanol.4
However, there is some speculation that a small amount of ethanol may be necessary
to ensure the quality of the baker’s yeasts.The oldest and first well-known industrial application of a fed-batch operation was
introduced after the end of World War I. It was the yeast cell production in which
sugar (glucose) was added incrementally during the course of fermentation to maintain
a low sugar concentration to suppress alcohol formation. The manufacture
of yeast by fed-batch culture has gone through a series of improvements and is an
industrially important fed-batch process. This process was historically followed by
penicillin fermentation, in which the energy source (e.g., glucose) and precursors
(e.g., phenyl acetic acid) were added incrementally during the course of fermentation8
to improve penicillin production. Prior to this practice, a slowly metabolized
but more expensive substrate, lactose, was used in place of glucose in a batch culture.
Oversupply of a carbon source resulted in more mycelial growth and low penicillin
formation, while undersupply resulted in slower mycelial growth and, eventually,
slower penicillin formation.The primary candidates in the list of
compounds that may be fed during the course of the operation include the limiting
substrate, inducers, precursors, a carbon source, a nitrogen source, a phosphate
source, inducers, and other nutrient sources. The feeding patterns are open loop
or feedback controlled to maintain some key variables at constant optimum values
such as the specific growth rate, respiratory quotient, pH, partial pressure of carbon
dioxide, dissolved oxygen, substrate concentration, and some metabolite concentrations.
The optimum feed rates sometimes require keeping these parameters to
follow certain optimum profiles rather than keeping them at constant values.
To maximize the cell formation rate for the case of constant cell mass yield, it
is obvious that the substrate concentration should be maintained at the value that
maximizes the specific growth rate, Sm, until the reactor is full. Therefore, it is also
obvious that the initial substrate concentration should be Sm, that is, S(0) = Sm,
and that the substrate concentration should be maintained at Sm throughout the
course of fermentation. This will lead to the maximum cell concentration at the
end of the run. To achieve this, the feed rate must be regulated properly to hold
the substrate concentration constant at Sm. If it is not possible to set the initial
substrate concentration to Sm for one reason or another, the substrate concentration
should be brought to this value as soon as possible by applying at the beginning the
maximum substrate feed rate (S(0) < Sm) or a batch period (S(0) > Sm) and then
regulating thereafter to maintain the substrate concentration to remain at Sm until
the fermentor is full. Once the fermentor is full, it is run in a batch mode to reduce
the substrate concentration to a desired level, and the cells containing the product
are harvested. This is the basis for the simplest case of a fed-batch culture. Initial establishment of fed batch is in BATCH mode and then the feeding is done by applying one of several strategies. lets see the strategies.... Quite interesting..uhmm1.Use the same medium which you have used to establish the batch culture and add it. what will happen? increase in volume.. right???2.Take the solution of limiting substrate; keeping concentration same as it was in initial medium & add it... again . tell me the result.... increase in volume... yes ! exactly..

Fed batch using above two strategies will be described as Variable Volume Fed Batch Culture

3.In this strategy concentrated solution of limiting substrate is to be added but at a rate less than no.1 & 2 strategy with the result is increase in volume.

So now we have an idea that what the heck is this fed batch strategy ..lets move on to the devilish part that is kinetics!!!! Start with Variable Volume Fed Batch culture

Variable Volume Fed Batch Culture

Pirt the king of kinetics ( That's what i call him......) , Dunn & Mor has developed this culture. I'm discussing Pirt's kinetics only. He said consider a batch culture in which growth is limited by concentration of one substrate; so whats the equation if we want to describe the biomass at any point of time::::

Equation for fed batch kinetics (variable volume)

Thus from above equation it may be concluded that input of substrate is compensated by substrate consumption. Thus ds/dt =0

Total biomass (X) concentration increases with time but cell concentration (x) remains constant, i.e. dx/dt = 0 and we can now write

μ= D

This situation is quasi steady state

(P.S. ::: please go back to basics of kinetics if you have trouble following above equation.. )

The difference between steady state in chemostat and quasi steady statein fed batch is that μ is constant in chemostat and it decreases in fed batch.

Fixed volume in next blog ....till then understand it and let me know if youy face any issues

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About Me

Myself a researcher interested in the field of genomics and biotechnology. Apart from following my dreams i also like to engage myself in helping other newbies in the field of life sciences. This blog is just a beginning to help budding scientists; who can get full fledged notes on biotech concepts. i have tried to make concise, thoroughly explained and supported with diagrams wherever necessary.This blog helps you avoid surfing websites for the conceptual notes. I am open to the suggestions and improvements!!! Good luck and Happy learning!!!